Unsaturated acids derived from polyacetylenic compounds



United States Patent 3,299,111 UNSATURATED ACIDS DERIVED FROMPOLYACETYLENIQ COMPUUNDS Bobby F. Adams, Painesvilie, Uhio, and John H.Wotiz,

Huntington, W. Va, assignors to Diamond Alkaii Company, Cieveland,(Bhio, a corporation of Delaware No Drawing. Filed Jan. 2, 1963, Ser.No. 248,861 3 Claims. (Cl. 260-413) This invention relates to newcompositions of matter, and in particular to novel compounds representedby the wherein R and R are selected from the group consisting ofhydrogen, alkyl (e.g., methyl, ethyl, n-propyl, isopropyl, butyl),amino-alkyl, carbamato-alkyl, COOR and @o H H H R NHOOONHaR- [(C=CRC::CR C=C-R wherein R and R are divalent hydrocarbon radicals containingstraight chains of at least one carbon atom; R is selected from thegroup consisting of hydrogen, alkyl, aryl (e.g., phenyl, naphthyl andsubstituted derivatives thereof) and aralkyl (e.g., benzyl, phenethyland substituted derivatives thereof); m is a number from O to 1,inclusive; and n is a number from 1 to 100, inclusive.

Still more particularly, this invention relates to novel compoundsrepresented by the following formula wherein R and R7 are selected fromthe group consisting of hydrogen, carboxy, (CH NH (CHQ NHCOOH and x is anumber from 1 to 20, inclusive; and n is as defined hereinbefore.

Specific illustrative examples of compounds of this invention includethe following:

1-trans-7-t-rans-13, 19-eicosatetraene H on,=on[(onnfi=o] (GI-mic IT=CH2 trans-Z-trans-S-trans-l4,20-heneicosatetraene-l-oic acid COOHl-amino-trans-5,1l-dodecadiene H CIIQZCI'I(CI'IZ)4ICI'=O (0119mmtrans5,1 1-dodecadienylammonium-trans-5,l1-

dodecadienylcarbamate 1,l6-diamino-trans-S-trans-1l-hexadecadiene HIl2N[(CII2l4IQ=C (0119mm l6amino-trans-5-trans-1l-hexadecadienylcarbamicacid Compounds of this invention may be prepared from polyacetyleniccompounds of the formula wherein R R R R m and n are as definedhereinbetriple bonds.

solved in liquid ammonia.

Normally, when pure sodium is added to liquid ammonia, it dissolves andforms a blue solution from which metallic sodium may be recovered byallowing the ammonia to evaporate. On the other hand, the addition of asmall amount of a ferric salt and the passage of air for a very shorttime through the solution results in the oxidation of the sodium tosodamide, with simultaneous liberation of hydrogen.

It is the blue solution of elemental sodium which is used in the processof this invention. Generally, enough sodium is used to furnish a to 200percent excess over the stoichiometric amount required for reduction ofall The stoichiometric amount is two gramatoms of sodium pergram-equivalent of polyacetylenic compound. It is usually convenient toadd the compound to be reduced slowly to the sodium solution; ifdesired, the compound to be reduced may be dissolved in an inertsolvent, such as ether, hexane, dioxane, or the like. However, theinverse method of addition also may be employed; that is, thepolyacetylenic compound may be added to the liquid ammonia first,followed by gradual addition of the sodium. The reduction is sometimescarried out in the presence of a lower alkanol, such as methanol, orammonium ions, e.g., ammonium sulfate.

After the reagents have all been added, the mixture is usually stirredfor some time, e.g., 30 minutes to 8 hours, after which the ammonia isallowed to evaporate and the reaction mixture is decomposed by thecautious addition of water, alcohol, or the like. The desired productmay then be isoalted and purified by distillation or recrystallizationif desired.

Amines of this invention are usually quite susceptible to reaction withcarbon dioxide and must be kept out of contact with the atmosphere. Theymay be converted into the respective carbamic acid derivatives bytreatment, either in the free state or in solution, with carbon dioxide.

The compounds of this invention are effective as pesticides forcontrolling fungi, bacteria, smuts, mildew, nematodes and otherorganisms in the class of plant pests.

While it is possible to apply the compounds of the present invention inundiluted form to the plant or other material to be protected, it isfrequently desirable to apply the novel compounds in admixture witheither solid or liquid inert, pesticidal adjuvants. Thus, the compoundscan be applied to the plants for fungicidal purposes, for example, byspraying them with aqueous or organic solvent dispersions of thecompound. Similarly, wood surfaces can be protected by applying aprotective film of the compound by brushing, spraying, or dippingutilizing a liquid dispersion of the compound. The choice of anappropriate solvent is determined largely by the concentration of activeingredient which it is desired to employ, by the volatility required ina solvent, the cost of the solvent and the nature of the material beingtreated. Among the many suitable organic solvents which can be employedas carriers for the present pesticides, there may be mentionedhydrocarbons, such as benzene, toluene, xylene, kerosene, diesel oil,fuel oil, petroleum, naphtha; ketones such as acetone, methyl ethylketone and cyclohexanone; chlorinated hydrocarbons such as carbontetrachloride, chloroform, trichloroethylene, perchlorethylene, esterssuch as ethyl acetate, ainyl acetate and butyl acetate, the m-onoalkylethers of ethylene glycol, e.g., the monomethyl ethers and the monoalkylethers of diethylene glycol, e.g., the monoethyl ether, alcohols, suchas ethanol, isopropanol and amyl alcohol, etc.

The compounds can also be applied to plants and other materials alongwith inert solid fungicidal adjuvants or carriers such as talc,pyrophyllite, attaclay, kieselguhr, chalk, diatomaceous earth, lime,calcium carbonate, bentonite, fullers earth, cotton-seed hulls, wheatflour, soybean flour, etc., pumice, tripoli, wood flour, walnut shellflour and lignin.

It is frequently desirable to incorporate a surface active agent in thepesticidal compositions of this invention. Such surface active agentsare advantageously employed in both the solid and liquid compositions.The surface active agent can be anionic, cationic or nonionic incharacter.

Typical classes of surface active agents include alkyl sulfonates,alkylaryl sulfonates, alkyl sulfates, alkylamide sulfonates, alkylarylpolyether alcohols, fatty acid esters of polyhydric alcohols, ethyleneoxide addition products of such esters; addition products of long chainmercaptans and ethylene oxide; sodium alkyl benzene sulfonates having 14to 18 carbon atoms, alkyl-phenolethylene oxides, e.g., p-isooctyl phenolcondensed with 10 ethylene oxide units; and soaps, e.g., sodium stearateand sodium oleate.

The solid and liquid formulations can be prepared in any suitablemethod. Thus, the active ingredients, in finely divided form if a solid,may be tumbled together with finely divided solid carrier.Alternatively, the active ingredient in liquid form, includingsolutions, dispersions, emulsions and suspensions thereof, may beadmixed with the solid carrier in finely divided form in amounts smallenough to preserve the free-flowing property of the final dustcomposition.

When solid compositions are employed, in order to obtain a high degreeof coverage with a minimum dosage of the formulation, it is desirablethat the formulation be in finely divided form. The dust containingactive ingredient usually should be sufficiently fine that substantiallyall will pass through a 20-mesh Tyler sieve. A dust which passes througha ZOO-mesh Tyler sieve also is satisfactory.

For dusting purposes, preferably formulations are employed in which theactive ingredient is present in an amount of 5 to 50% of the total byweight. However, concentrations outside this range are operative andcompositions containing from 1 to 99% of active ingredient by weight arecontemplated, the remainder being carrier and/ or any other additive oradjuvant material which may be desired. It is often advantageous to addsmall percentages of surface active agents, e.g., 0.5 to 1% of the totalcomposition by weight, to dust formulations, such as the surface activeagents previously set forth.

For spray application, the active ingredient may be dissolved ordispersed in a liquid carrier, such as water or other suitable liquid.The active ingredient can be in the form of a solution, suspension,dispersion or emulsion in aqueous or non-aqueous medium. Desirably, 0.5to

1.0% of a surface active agent by weight is included in the liquidcomposition.

For adjuvant purposes, any desired quantity of surface active agent maybe employed, such as up to 250% of the active ingredient by weight. Ifthe surface active agent is used only to impart wetting qualities, forexample, to the spray solution, as little as 0.05% by weight or less ofthe spray solution need be employed. The use of larger amounts ofsurface active agent is not based upon wetting properties but is afunction of the physiological behavior of the surface active agent.These considerations are particularly applicable in the case of thetreatment of plants. In liquid formulations the active ingredient oftenconstitutes not over 30% by Weight of the total and may be or even aslow as 0.01%.

The novel compounds of the present invention can be employed incompositions containing other pesticides,

more especially fungicides, insecticides and bactericides, e.g.,phenothiazine, pyrethrum, rotenone, DDT, etc.

The following examples are offered in order that those skilled in theart may achieve a fuller understanding of the invention and thepreferred methods by which the same may be carried into effect. Itshould be understood, however, that the invention is not to be limitedby these examples, since modifications thereof may be made which arewithin the full intended scope of the invention as defined in theappended claims.

EXAMPLE 1 Preparation of 1,7,13,]9-eic0satetrayne A five-liter,three-necked flask, equipped with a stirrer, Dry Ice condenser and gasinlet tube, is charged with 3 liters of liquid ammonia and 234 g. (6moles) of sodamide. Four and one-half moles of acetylene is measuredinto the stirred suspension at which point the mixture begins to clear,and then the gas inlet tube is replaced by an addition funnel and 648 g.(3 moles) of 1,4-dibromobutane is added slowly as stirring is continued.

The ammonia is allowed to evaporate overnight and the residual mixtureis hydrolyzed by cautious addition of about 300 ml. of water. Theaqueous and organic layers are separated and the aqueous layer isextracted several times with ml. portions of ether. The ether extractsand organic layer are combined, washed with 5 percent aqueous solutionsof hydrochloric acid and sodium carbonate and dried over calciumsulfate.

After removal of the ether by evaporation, the residue is distilledunder reduced pressure. The desired 1,7,13,l9-eicosatetrayne boils at toC. per 0.3 mm. Hg.

EXAMPLE 2 Preparation of 1 -trans-7-trans-13,1 9-eic0saletraene To astirred solution of 74 .g. (3.2 gram-atoms) of sodium in 1 liter ofliquid ammonia is slowly added a solution of 53.3 g. (0.2 mole) of1,7,13,19-eicosatetrayne in 150 ml. of anhydrous ether. The mixture isstirred for one hour, and then 300 ml. of water is added cautiously. Theammonia is allowed to evaporate overnight, and the remaining equeoussuspension is extracted with ether. The ether extracts are dried overcalcium chloride and concentrated. There is obtained 52.5 g. of an amberliquid which is shown by infrared and vapor phase chromatographicanalysis to be a mixture of four components, the mixture containing bothtriple and trans-double bonds.

A portion (21.8 g.) of this mixture is dissolved in 96 g. of methanoland 1 liter of liquid ammonia and further reduced by inverse addition of57.5 g. (2.5 gram-atoms) of sodium. After workup, the product (19.8 g.)contains two components. It is further reduced by the inverse additionmethod using 128 g. of methanol and 69 g. (3 gram-atoms) of sodium. Theproduct, 1-trans-7-trans- 13,19-eicosatetraene, is distilled, B.P.129-130 C. per 0.5 mm. Hg. The yield is 17.5 g. of pure material asshown by infrared and vapor phase chromatographic analysis.

Analysis for C H Calculated: C, 87.5%; H, 12.5%. Found: C, 87.3%;H,12.4%.

EXAMPLE 3 Preparation of 2,8,14,20-11eneicosatetrayne-I -01'c acid Threemoles of 1,7,13,l9-eicosatetrayne disodium salt is prepared from 798 g.(3 moles) of 1,7,13,19-eicosatetrayne and 7 moles of NaNH in 3.5 litersof anhydrous ammonia. The ammonia is replaced 'by 6 gallons of a 1:1:1(by volume) mixture of benzene, ethyl ether and tetrahydrofuran and thesuspended salt is pressurized with CO at 25 C. and 500 psi. in a10-gallon autoclave for 60 hours. After venting, the mixture ishydrolyzed with 1 gallon of water. The organic layer is separated anddried and the solvent is evaporated; there is recovered 354 g. of impureunreacted 1,7,13,19-eicosatetrayne. The aqueous solution is acidifiedwith hydrochloric acid and the precipitated solid is extracted withether. After evaporation of the ether the residue is treated withpentane in .a Soxhlet extractor, yielding 133 g. (26% conversion) ofsoluble white product, M.P. 5455 C. which is identified as2,8,14,20-heneicosatetrayne-l-oic acid. The results of the chemicalanalysis indicate the formation of the desired C H O and are as follows:

The actual neutralization equivalent found is 313, while the calculatedvalue is 310. The infrared spectrum is consistent with the assignedstructure.

EXAMPLE 4 Preparation f trans-2-trans-8-trans-14,20-heneic0-satetraene-J-oic acid A solution of 23.2 g. (0.08 mole) of2,8,14,20-heneicosatetrayne-l-oic acid in 150 ml. of anhydrous ether isadded rapidly to a stirred solution of 46 g. (2 gramatoms) of sodium in1 liter of liquid ammonia. The mixture is stirred for one and one-halfhours and hydrolyzed by the cautious addition of 150 ml. of water. Theammonia is allowed to evaporate overnight and the residue is poured intoa slurry of concentrated hydrochloric acid and ice. The solid whichprecipitates is extracted with ether and the extracts are washed withwater and dried over calcium chloride.

The ether is removed by evaporation, leaving a yellow oil whichsolidifies at about 11 C. The infrared spectrum is in agreement with theassigned structure of trans-2-trans-8-trans-14,20-heneicosatetraene-1-oic acid. The yield is 21.5g., or 90% of the theoretical amount.

Analysis for C H O Calculated: C, 79.1%; H, 10.7%; neutral equivalent,318%. Found: C, 78.8%; H, 10.5%; neutral equivalent, 336%.

EXAMPLE 5 Preparation of 1,16-diamin0-5,1J-hexadecadiyne and I-amino-5,1I-doa'ecadiyne 1,7-octadiyne, 630 g. (6 moles), is added to asuspension of 468 g. (12 moles) of sodarnide in one gallon of liquidammonia. The resulting suspension of 1,7-octadiyne disodium salt isadded in portions to a solution of 2592 g. (12 moles) of1,4-dibromobutane in 2 gallons of liquid ammonia in a 5-gallon stirredautoclave. The mixture is stirred for three hours, and then theautoclave is sealed and heated to 50 C. for three hours. The mixture iscooled and the autoclave is vented. After most of the ammonia hasevaporated, the residue is diluted with water and extracted with 5liters of ether. Carbon dioxide is passed through the ether solution andthe resulting precipitate is filtered. Upon treatment of the solids withaqueous sodium hydroxide solution, the desired1,16-diamino-5,1l-hexadecadiyne separates as an oil. It is dried out ofcontact with air and distilled, B.P. 152 C./0.05 mm. Hg. The product isvery sensitive to atmospheric carbon dioxide and must be kept out ofcontact with it.

The ethereal filtrate from the carbon dioxide treatment is distilled.After removal of the ether, the desired 1- amino-5,11-dodecadiyne isobtained, B.P. 82-85 C. per 0.05 mm. Hg.

EXAMPLE 6 Preparation of 1-c1min0-trans-5,11-d0decadiene A solution of53.2 g. (0.3 mole) of 1-amino-5,11- dodecadiyne in ml. of anhydrousether is added slowly, with stirring, to a solution of 55.2 g. (2.4gram-atoms) of sodium in 1 liter of liquid ammonia. The mixture isstirred for one hour, after which 300 ml. of water is added cautiously.The bulk of the ammonia is allowed to evaporate and the residue isextracted with ether. The ether extracts are washed with water and driedover calcium sulfate, and the ether is removed by evaporation. Upondistilling the residue (46.8 g.) at reduced pressure under nitrogen,there is obtained 99 percent pure (by vapor phase chromatographicanalysis) 1-an1ino-trans-5,11-dodecadiene, B.P. 73-74 C. per 0.6 mm. Hg.The product is very sensitive to atmospheric carbon dioxide.

Analysis for C H N. Calculated: C, 79.5%; H, 12.8%; N, 7.7%. Found: C,79.2%; H, 12.9%;N, 8.1%.

EXAMPLE 7 Preparation 0] trans-5 ,1 1 -dodecadieny[ammonium-trans-5,11-d0tlecaa'z'eny lcarbanzate Thirty grams of1-amino-tr=ans-5,1l-dodecadiene is placed in a Petri dish and exposed tocarbon dioxide. A solid is formed (about 35 g) which decomposes whentreated with solvents, but forms again upon evaporation of the solvent.Infrared and elemental analysis confirm the assigned structure astrans-5,11-dodecadienylammonium-trans-5,1l-dodecadienylcarbamate.

Analysis for C H N O Calculated: C, 73.8%; H, 11.4%; N, 6.9%. Found: C,74.0%; H, 10.9%; N, 8.1%.

EXAMPLE 8 Preparation 0 1,16-diamin0-trans-5-trans II-hexadecadiene To astirred suspension of 38.4 g. of methanol and 24.8 g. (0.1 mole) of1,l6-diamino-5,ll-hexadecadiyne in 1 liter of liquid ammonia is added,in small portions, 18.4 g. (0.8 gram-atom) of sodium. Stirring iscontinued for one-half hour, and the mixture is then cautiously dilutedwith 400 ml. of water. The ammonia is allowed to evaporate and theresidue is extracted with ether. Upon purification as in Example 6, thedesired 1,16-diamino-trans- 5-tr ans-l1-hexadecadiene is obtained, B.P.146 to 148 C. per 0.5 mm. Hg, M.P. 31 to 33 C. The product is verysensitive to carbon dioxide.

Analysis for C H N Calculated: C, 76.2%; H, 12.8%; N, 11.1%. Found: C,76.5%; H, 12.5%; N, 11.3%.

EXAMPLE 9 Preparation 0 f 16-amino-trans-S-trans-I1-hexadecadienylcarbamic acid Calculated: C, 68.9%; Found: C, 68.8%; H,10.8%;

7 EXAMPLE 10 F zmgicidal activity The tomato foliage disease testmeasures the ability of the test compound to protect tomato foliageagainst infection by the early blight fungus Alternaria solani and thelate blight fungus P/zytoplzlhora infestans. Results from this testindicate whether a compound may have practical use as a foliageprotectant fungicide.

The method used employs tomato plants (var. Bonny Best) five to seveninches high which are four to six weeks old. Duplicate plants, one setfor each test fungus, are sprayed with 100 ml. of the test formulationat 40 pounds air pressure as the plants are rotated on a turntable in ahood. The center of the turntable is 45 inches from the nozzle of thespray gun.

The test formulations used in this procedure contain 1000 p.p.m. and 200ppm, respectively, of the compound being tested and are prepared bymixing 0.1 g. of the test compound, 4 ml. of acetone and 2 ml. of astock solution of Triton X-155 emulsifier in water (0.5% Triton Xl55 byvolume), and diluting with water to 100 ml. This solution is useddirectly for the 1000 p.p.m. test, and is diluted with water to 20% forthe 200 p.p.m. test.

After the spray deposit is dry, treated plants and controls (sprayedwith formulation less toxicant) are sprayed while being rotated on aturntable with a spore suspension containing a proximately 20,000conidia of A. solani per ml., or 150,000 sporangia of P. infestans perml. The atomizer used delivers 20 ml. in the 30-second exposure period.The plants are held in a saturated atmosphere for 24 hours at 70 F. forearly blight and 60 F. for late blight to permit spore germination andinfection before removal to the greenhouse.

After two days from the start of the test for early blight and threedays for late blight, lesion counts are made on the three uppermostfully expanded leaves. The data are converted to percentage diseasecontrol based on the number of lesions obtained on the control plants.

The following table gives the responses of several of the compounds ofthis invention when tested by this method.

Bactericidal activity Test chemicals are examined for ability to inhibitthe growth of four bacterial species (Erwinia amylovora, Xantlzomonasphaseoli, MicrocOccl/s pyogenes var. am'cus, Escherechia coli) at aconcentration of 250 p.p.m. The first two and fourth above-named testspecies are gram negative rods, the third species is gram positive. Theyare all cultured on nutrient agar slants except X. phaseoli which isgrown on potato dextrose agar. The cultures used for tests aresub-cultured for two sequential 24-hour periods to insure uniform testpopulations. Bacterial suspensions are made from the second sub-culture6 in the culture tube by addition of distilled water and gentleagitation after which they are filtered through double layers ofcheesecloth and adjusted to standard concentrations by turbidimetricmeasurement.

Each of four test tubes arranged in a rack receive one ml. of the testformulation which is prepared by mixing 0.1 g. of the test compound, 4ml. of acetone and 2 ml. of the stock solution of Triton X-155emulsifier (see Example 10) and diluting with water to ml.

After the test formulations have been measured into a test tube, 3% ml.of distilled water and /2 ml. of bacterial suspension for eachrespective test organism is added to each test tube. (The finalconcentration of the test chemical is 250 p.p.m.) The medication tubesare then set aside at room temperature for four hours. After thisexposure period transfers are made by means of a standard four mm.platinum loop to 7 ml. of sterile broth in test tubes arranged in rackssimilar to those for the medication tubes. The broth tubes are thenincubated for 48 hours at 29 to 31 C. at which time growth is measuredby use of a Bausch and Lomb spectronic 20 direct reading colorimeter. Areading is recorded for each test tube after shaking. Usually threereplicates of each organism serve as controls. Calculations are made onpercent of the mean check readings. This figure subtracted from givespercent control as compared to checks.

The following four compounds are 100% effective against all four speciesof bacteria when tested by this method: 1-arnino-trans-5,ll-dodccadiene;1,16-diaminotrans 5-trans-1l-hexadecadiene;trans-5,11-dodecadienylammonium trans-5,1l-dodecadienylcarbamate;16-aminotrans-S-trans-ll-hexadecadienylcarbamic acid.

What is claimed is:

1. Compounds of the formula wherein R is selected from the groupconsisting of hydrogen and carboxy; R is carboxy; n is an integer from 2to 100, inclusive; and x is an integer from 1 to 20, inclusive. 2. Thecompounds of claim 1 wherein R is hydrogen and x is the integer 4.

3. Trans 2-trans-8-trans-14,20-heneicosatetraene-l-oic acid.

References Cited by the Examiner UNITED STATES PATENTS 2,895,869 7/1958Bluestone 167-22 2,934,570 4/1960 Goldberg et a1. 260413 X 3,016,3271/1962 Schmitz et al. 16722 3,031,512 4/1962 Osbond et al 260413 X3,032,491 5/1962 Barton et a1 260413 X 3,032,583 5/1962 Chiusoli et al.260413 X 3,033,884 5/1962 Osbond et a1 260413 3,052,699 9/1962 Beal260413 3,053,868 9/1962 Schmerling et al. 260413 OTHER REFERENCES Fieseret al.: Advanced Organic Chemistry, N.Y., Reinhold, 1961 pp. 229 and230.

Whitmore: Organic Chemistry, N.Y., D. Van Nostrand, 1937, p. 50.

CHARLES B. PARKER, Primary Examiner.

G. MENTIS, R. L. RAYMOND, Assistant Examiners.

1. COMPOUNDS OF THE FORMULA